{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T05:01:07Z","timestamp":1790226067523,"version":"4.1.0"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    The role of UBE2N in myeloid cell-mediated immune suppression in cancer remains undefined. Here, we examined the function of UBE2N in myeloid cell-mediated tumor progression using a temporally inducible myeloid-specific knockout model (\n                    <jats:italic>\n                      LysM\n                      <jats:sup>CreER<\/jats:sup>\n                      Ube2n\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    ). Temporally induced deletion of\n                    <jats:italic>Ube2n<\/jats:italic>\n                    in myeloid cells (\n                    <jats:italic>\n                      Ube2n\n                      <jats:sup>MyeKO<\/jats:sup>\n                    <\/jats:italic>\n                    ) significantly hindered growth of YUMM1.7 melanoma. This was accompanied by reduced myeloid cell burden within the tumor microenvironment. We observed altered abundance of PD-1, PD-L1, and SPP1 in the\n                    <jats:italic>\n                      Ube2n\n                      <jats:sup>MyeKO<\/jats:sup>\n                    <\/jats:italic>\n                    tumor microenvironment at the tissue level.\n                    <jats:italic>In vitro<\/jats:italic>\n                    analysis showed that knock-in expression of a catalytically deficient UBE2N\n                    <jats:sup>C87S<\/jats:sup>\n                    mutant in bone marrow-derived macrophages (BMDMs) markedly decreased expression of\n                    <jats:italic>Spp1<\/jats:italic>\n                    . We observed decreased SPP1 secretion in\n                    <jats:italic>\n                      Ube2n\n                      <jats:sup>MyeKO<\/jats:sup>\n                    <\/jats:italic>\n                    BMDM-conditioned media (CM). Treatment with\n                    <jats:italic>\n                      Ube2n\n                      <jats:sup>MyeKO<\/jats:sup>\n                    <\/jats:italic>\n                    BMDM-CM decreased co-expression of PD-1, TIM-3, and LAG-3 on chronically stimulated T cells. Antibody-mediated neutralization of SPP1 in\n                    <jats:italic>\n                      Ube2n\n                      <jats:sup>MyeWT<\/jats:sup>\n                    <\/jats:italic>\n                    BMDM-CM decreased PD-1 expression on CD8+ T cells. Together, these findings suggest a role for myeloid UBE2N in YUMM1.7 progression.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2026.1932270","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T04:32:38Z","timestamp":1790224358000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Conditional myeloid-specific deletion of Ube2n hinders YUMM1.7 melanoma growth"],"prefix":"10.3389","volume":"16","author":[{"given":"Kelsie","family":"Schiavone","sequence":"first","affiliation":[{"name":"Department of Dermatology, Duke University Medical Center","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Pecoraro","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Duke University Medical Center","place":["Durham, NC, United 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